VAP-1, Eotaxin3 and MIG as potential atherosclerotic triggers of severe calcified and stenotic human aortic valves: Effects of statins

Thomas Anger*, Falk K. Pohle, Lukas Kandler, Thomas Barthel, Stephan M. Ensminger, Theodor Fischlein, Michael Weyand, Christian Stumpf, Werner G. Daniel, Christoph D. Garlichs

*Korrespondierende/r Autor/-in für diese Arbeit
23 Zitate (Scopus)

Abstract

Sclerotic calcification of the aortic valve is a common disease in advanced age. Its pathophysiology is unclear. However, pathobiological similarities to atherosclerosis have been shown in several studies. The current study assesses gene profiling of severe calcified stenotic human aortic valves identifying transforming growth factor (TGF)-β, Eotaxin3, vascular adhesion protein-1 (VAP-1) and monokine induced by interferon-γ (MIG) as potential atherosclerotic target genes in severe calcified and stenotic aortic valves, and analyzes the effects of statins on their expression as part of an anti-inflammatory treatment strategy. We collected human severe calcified and stenotic aortic valves with (CSAV+) or without (CSAV-) statin pre-treatment prior to valve replacement and investigated gene profiling by using micro-array technique and real-time PCR for the TGF-β, Eotaxin3, VAP-1 and MIG expression. In comparison to atherosclerotic plaques of carotid arteries, immunohistochemical staining was investigated. Results were contrasted to human normal non-calcified aortic valves as controls (C). As compared to C, TGF-β, Eotaxin3, MIG or VAP-1 was significantly upregulated in CSAV-. In CSAV+ no significant change in gene expression was found for Eotaxin3 and MIG. In contrast, VAP-1 and TGF-β were still upregulated. Corresponding gene expression was confirmed on atherosclerotic plaque formations of carotid arteries. Monocyte/Macrophage infiltration (presence of CD68) on aortic valves (CSAV+, CSAV-, or C) confirmed inflammatory nature of the disease. Our data support further evidence for atherosclerotic inflammation as a trigger for sclerosis in end-stage calcified stenotic aortic valves by showing upregulation of gene expression for TGF-β, VAP-1, MIG and Eotaxin3, which is only partially inhibited by previous statin therapy. Potent benefits of statin treatment on early stages of valve disease are still propagated.

OriginalspracheEnglisch
ZeitschriftExperimental and Molecular Pathology
Jahrgang83
Ausgabenummer3
Seiten (von - bis)435-442
Seitenumfang8
ISSN0014-4800
DOIs
PublikationsstatusVeröffentlicht - 12.2007

Fingerprint

Untersuchen Sie die Forschungsthemen von „VAP-1, Eotaxin3 and MIG as potential atherosclerotic triggers of severe calcified and stenotic human aortic valves: Effects of statins“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitieren